rs1219265957

Variant names:

• chr20-59605061-G-A
• NM_080672.5:c.47G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-59605061-G-A
• chr20-59605061-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_080672.5(PHACTR3):​c.47G>A​(p.Arg16His) variant causes a missense change. The variant allele was found at a frequency of 0.0000016 in 1,251,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: PHACTR3 NM_080672.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.40

Genes affected

PHACTR3 (HGNC:15833): (phosphatase and actin regulator 3) This gene encodes a member of the phosphatase and actin regulator protein family. The encoded protein is associated with the nuclear scaffold in proliferating cells, and binds to actin and the catalytic subunit of protein phosphatase-1, suggesting that it functions as a regulatory subunit of protein phosphatase-1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39213225).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHACTR3	NM_080672.5	c.47G>A	p.Arg16His	missense_variant	Exon 1 of 13	ENST00000371015.6	NP_542403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHACTR3	ENST00000371015.6	c.47G>A	p.Arg16His	missense_variant	Exon 1 of 13	1	NM_080672.5	ENSP00000360054.1
PHACTR3	ENST00000434923.1	c.47G>A	p.Arg16His	missense_variant	Exon 3 of 4	5		ENSP00000390915.1
PHACTR3	ENST00000359926.7	c.109+27444G>A		intron_variant	Intron 1 of 12	2		ENSP00000353002.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000160 AC: 2 AN: 1251032 Hom.: 0 Cov.: 41 AF XY: 0.00 AC XY: 0 AN XY: 610968

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000171

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.96e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	.;T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.76	T;D
M_CAP	Pathogenic	0.53	D
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-0.80	T
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-5.0	D;N
REVEL	Benign	0.11
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.37
MutPred		0.24		Gain of catalytic residue at R14 (P = 0.0977);Gain of catalytic residue at R14 (P = 0.0977);
MVP		0.37
MPC		0.25
ClinPred		1.0	D
GERP RS		4.3
Varity_R		0.27
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-58180116;